The c-Met–directed ADC-based combination was designated for mCRC previously treated with fluoropyrimidine, irinotecan, oxaliplatin, and anti-VEGF therapy.
The FDA has granted breakthrough therapy designation to telisotuzumab adizutecan (Temab-A; ABBV-400) in combination with bevacizumab (Avastin) for the treatment of adult patients with refractory metastatic colorectal cancer (mCRC) who have previously received fluoropyrimidine, irinotecan, oxaliplatin, an anti-VEGF monoclonal antibody, and, if indicated, an anti-EGFR monoclonal antibody.¹
The designation was primarily based on data from the first-in-human phase 1 study M21-404 (NCT05029882). In the Temab-A/bevacizumab combination cohort of that trial, data presented at the
“As one of the most advanced assets in our next-generation antibody-drug conjugate [ADC] portfolio, Temab-A has demonstrated potential across multiple tumor types, both as a monotherapy and in combinations,” Eleni Lagkadinou, MD, PhD, vice president of oncology early development at AbbVie, stated in a news release.1 “We believe [this designation] further [supports] our strategy of advancing biomarker-driven therapies and [underscores] our commitment to developing transformative medicines for patients with difficult-to-treat cancers.”
Temab-A is an investigational c-Met–directed ADC with a topoisomerase 1 inhibitor payload.1
Temab-A Plus Bevacizumab in Refractory mCRC: Highlights
The combination cohort enrolled biomarker-unselected patients with advanced CRC in a safety lead-in portion followed by a dose-optimization phase, in which patients were randomly assigned to receive Temab-A at 2.0 mg/kg or 2.4 mg/kg plus bevacizumab at 7.5 mg/kg every 3 weeks, or SOC TAS-102 plus bevacizumab at 5.0 mg/kg every 2 weeks.²
In the pooled Temab-A patient population in study M21-404 (n = 63), the most frequently reported treatment-emergent adverse effects (TEAEs) were anemia (grade 1/2, 12%; grade ≥ 3, 37%), neutropenia (13%; 16%), thrombocytopenia (17%; 5%), nausea (60%; 0%), decreased appetite (33%; 2%), fatigue (41%; 8%), vomiting (40%; 2%), diarrhea (24%; 0%), constipation (24%; 2%), and cough (25%; 0%). Hematologic TEAEs were reported to be dose dependent and occurred at an increased frequency with higher Temab-A doses. Notably, the overall rate of adjudicated ILD/pneumonitis among patients who received Temab-A was 5% (n = 3); 1 of these patients had a grade 3 event, and no grade 4 or 5 events were observed.
The phase 3 AndroMETa-CRC trial (NCT07525206) is an ongoing, open-label, randomized, controlled, global study comparing Temab-A plus bevacizumab vs TAS-102 plus bevacizumab in patients with refractory mCRC.3 Objectiveresponse rate and OS are the primary end points. Key secondary end points include OS stratified by c-Met expression, PFS, duration of response, and disease control rate.
Furthermore, Temab-A monotherapy received FDA breakthrough therapy designation for the treatment of adult patients with locally advanced or metastatic, EGFR wild-type c-MET protein–expressing, nonsquamous non–small cell lung cancer who have been previously treated with platinum-based chemotherapy and a PD-(L)1–directed antibody.1
